Androgenetic alopecia (AGA) manifests as progressive hair follicle (HF) miniaturization; however, its drivers remain poorly elucidated. Combining spatial and single-cell transcriptomics, we generate a concise single-cell atlas of anagen HFs in male AGA, revealing early changes in cell subpopulations, altered HF stem cell fate determination, and disrupted cell-cell communications. Through ex vivo HF organ culture and humanized mouse models, we demonstrate that hypercontractility of connective tissue sheath (CTS) activates the mechanosensitive channel PIEZO1 in anagen HFs. This mechanotransduction induces ectopic apoptosis of HF progenitor cells and suppresses matrix/ORS cell proliferation, depleting progenitor pools and impairing HF growth, thereby driving progressive miniaturization. Critically, pharmacological inhibition of CTS contraction via ML-7, a selective myosin light chain kinase (MLCK) inhibitor, improves HF growth in both male AGA patient-derived ex vivo models and humanized mice. Our study delineates the cellular dynamics underlying male AGA pathogenesis and identifies mechanopathologically activated CTS as a key driver of HF miniaturization, positioning the peri-follicular CTS as a promising therapeutic target for AGA intervention.

BACKGROUND:Routine laboratory monitoring is recommended during Janus kinase inhibitor therapy, but its clinical yield in patients with alopecia areata has not been prospectively characterized. OBJECTIVE:To characterize the incidence, timing, severity, and clinical significance of laboratory abnormalities during ritlecitinib treatment. METHODS:In this prospective cohort, patients aged 12 years or older received ritlecitinib 50 mg once daily. Complete blood count, liver, and renal function parameters were assessed. Treatment-emergent abnormalities were predefined using local reference intervals and graded using Common Terminology Criteria for Adverse Events 5.0. Exploratory Cox regression was performed to identify factors associated with first laboratory abnormality. RESULTS:Among 162 patients contributing 62.9 patient-years, 99 (61.1%) developed at least 1 treatment-emergent laboratory abnormality; 67 first events (67.7%) occurred within 3 months. Abnormalities were predominantly mild: 97 patients had maximum grade 1 abnormalities, 2 had grade 2 abnormalities, and none had grade 3 or higher abnormalities. Prior systemic treatment was associated with higher hazard on univariable analysis (hazard ratio, 1.52; 95% confidence interval, 1.02-2.28; P = .041), but no independent predictor remained after multivariable adjustment. LIMITATIONS:Single-center design, Chinese cohort, and incomplete scheduled monitoring. CONCLUSION:Laboratory abnormalities during ritlecitinib therapy were common but mild and rarely actionable, supporting potential reconsideration of monitoring intensity.

BACKGROUND:Alopecia areata (AA) is frequently associated with atopic and autoimmune comorbidities, yet comprehensive data in Chinese populations remain scarce. We aimed to characterize the comorbidity landscape and identify predictors of the total comorbidity count in AA patients. METHODS:In this cross-sectional study of 1008 AA patients, we assessed the prevalence of atopic and autoimmune comorbidities across different age groups and clinical subtypes. Predictors of the total comorbidity count were identified using multivariable negative binomial regression. RESULTS:Overall, 21.1% of patients presented with at least 1 comorbidity (14.7% atopic, 8.2% autoimmune). The comorbidity profile of AA exhibits significant age-specific distribution variations: younger patients are more frequently affected by atopic conditions, whereas autoimmune comorbidities progressively increase with advancing age, reflecting general population immunological trends. Furthermore, autoimmune comorbidities were significantly associated with the alopecia totalis subtype (22.5% vs 8.2% in the overall cohort; P = .013). Multivariable regression identified female sex (aIRR = 1.507, P = .003), pediatric age (aIRR = 1.553, P = .006), and notably, mild disease severity (Severity of Alopecia Tool <25; aIRR = 1.854, P = .011) as independent predictors of the total comorbidity count. CONCLUSION:The comorbidity profile of AA is defined by a striking age dichotomy: younger patients are predominantly predisposed to atopic conditions, whereas autoimmune comorbidities progressively emerge with advancing age. This age-specific transition strongly advocates for age-stratified, targeted screening strategies.

BACKGROUND:Alopecia areata (AA) is a chronic autoimmune condition that causes non-scarring hair loss and often leads to significant psychosocial distress. Although Janus kinase (JAK) inhibitors such as tofacitinib are effective, relapse after stopping treatment remains a major challenge. New evidence indicates that low-dose interleukin-2 (IL-2) may help maintain remission by increasing regulatory T cells, which can restore immune tolerance. OBJECTIVE:This proof-of-concept study aimed to evaluate the efficacy of sequential immunotherapy combining tofacitinib and low-dose IL-2 in inducing sustained remission for AA patients after treatment withdrawal. METHODS:A monocentric, retrospective case series was conducted at Xiangya Hospital, China, from September 2022 to May 2025. The IL-2 regimen comprised subcutaneous injections (0.5-1 million IU/day for 5 consecutive days per cycle), repeated every 3 weeks for two to three cycles. Tofacitinib was tapered and discontinued post-IL-2 therapy. Clinical outcomes, including relapse-free survival and safety, were monitored longitudinally. RESULTS:Four refractory AA patients (median follow-up: 32.5 months) with complete hair regrowth (SALT = 0) after ≥6 months of tofacitinib received adjunctive IL-2. Three patients maintained complete remission for 11-20 months after treatment cessation, while one experienced localized recurrence at 5 months but achieved control with low-dose tofacitinib maintenance. No adverse events were reported. CONCLUSION:Sequential tofacitinib and low-dose IL-2 therapy may reestablish immune tolerance, offering a potential strategy for drug-free remission. Larger trials are needed to confirm efficacy and optimize protocols.

BACKGROUND:Alopecia areata (AA) causes significant psychological distress. Standard assessments often classify patient stress as merely high or low, overlooking key differences in stress experiences, such as anxiety versus helplessness. This study employed a person-centered method to identify distinct subgroups of AA patients based on their unique patterns of anxiety-related stress. METHODS:A cross-sectional survey of adults with AA was conducted using the validated Chinese version of the 14-item Perceived Stress Scale (PSS-14). Latent profile analysis (LPA) was applied to the PSS-14 responses to identify distinct subgroups of stress experience. Multinomial logistic regression was then used to examine demographic and clinical predictors of subgroup membership. RESULTS:A total of 561 adult patients with AA were analyzed. LPA of the PSS-14 responses revealed three distinct stress profiles: a low-tension/low-loss-of-control group (42.4%), a high-tension/low-loss-of-control group (15.7%), and a low-tension/high-loss-of-control group (41.9%). Membership in the more distressed profiles was significantly associated with lower odds of having more severe disease (alopecia totalis/universalis), and sex was associated with membership in the high-tension/low-loss-of-control profile. No other clinical variables were significant. CONCLUSIONS:This study identified three distinct, clinically meaningful profiles of perceived stress in adults with AA. These findings demonstrate that psychological distress in AA is multifaceted and cannot be inferred from clinical severity alone. A more nuanced, profile-aware approach is advocated to tailor psychosocial support in clinical management.

Livedoid vasculopathy (LV) is a chronic microvascular thrombosis disorder with poorly understood pathogenesis, potentially involving hypercoagulability and inflammation. The aim of this study included analyzing the association between these indices and disease severity, as well as evaluating the real-world efficacy of rivaroxaban, to determine optimal personalized treatment strategies for LV. This retrospective analysis was conducted on 41 patients with LV and 19 healthy controls. Patients were treated with 10 mg daily rivaroxaban and assessed using the Livedoid Vasculopathy Activity/Severity Score and the Numerical Rating Scale. Thirty-two females (78.0%) were included, with a mean age of 26.1 years. The platelet count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR) and plateletcrit levels were significantly increased in patients with LV compared with those in healthy controls. Platelet count, plateletcrit and PLR positively showed a positive correlation with clinical severity scores, which can serve as simple and cost-effective measures for assessing disease severity. Rivaroxaban at 10 mg daily resulted in disease control in 78.0% of patients within 3 weeks. Patients with inadequate responses exhibited higher severity scores and required dose adjustments or combination therapy. Adverse effects were generally mild, comprising 6 instances of menorrhagia, 2 cases of bleeding hematochezia and 1 allergic reaction.

BACKGROUND:Despite the established therapeutic potential of ritlecitinib for alopecia areata (AA), real-world evidence regarding its effects on lipid metabolism remains limited. OBJECTIVE:To characterize the effects of ritlecitinib therapy on lipid profiles in patients with AA. METHODS:In this single-center retrospective cohort study, we evaluated 55 patients with AA who completed ≥24 weeks of ritlecitinib therapy. Fasting serum lipid parameters (total cholesterol, triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol, non-HDL-C), and atherogenic index of plasma (AIP) were assessed at baseline, 12, and 24 weeks. Comparative analyses were conducted between patients with normal versus abnormal baseline lipid profiles. RESULTS:Ritlecitinib therapy demonstrated stability across conventional lipid parameters throughout the 24 week observation period. A clinically significant reduction in AIP was observed at 12 weeks (median change: -0.31, 95% CI: -0.37 to -0.21; P < .05). Patients with baseline dyslipidemia exhibited progressive improvement in atherogenic lipid fractions, suggesting a potential therapeutic modulation of lipid metabolism. LIMITATIONS:Single-center and Chinese-limited cohort. CONCLUSION:These real-world data suggest ritlecitinib maintains a favorable lipid safety profile while potentially conferring metabolic benefits for AA patients with preexisting dyslipidemia.

Atmospheric CO2 concentrations are rising and projected to reach ∼800 μmol mol-1 by 2100, while soil salinity is expanding globally, yet their combined impact on crops remains unclear. In particular, the interactive effects of elevated CO2 and salinity on maize (Zea mays L.) physiology and development are poorly understood. The physiological and anatomical responses of maize to elevated CO2 (800 μmol mol-1) and NaCl stress (0-150 mmol L-1) were investigated through a controlled factorial experiment. Results showed that elevated CO2 increased net photosynthetic rate, water-use efficiency, and biomass accumulation, partially mitigating salt-induced reductions in growth and photosynthesis under moderate NaCl stress, while mitigating salt-induced growth inhibition through three key mechanisms: (1) reinforcement of antioxidant defenses and improve water use efficiency by upregulating superoxide dismutase and peroxidase, (2) osmotic adjustment via leaf non-structural carbon accumulation especially under moderate salinity, and (3) high salinity caused structural deteriorations such as thinner leaves, lower stomatal density, and reduced vascular bundle size, while elevated CO2 counteracted salinity-induced structural degradation, maintaining leaf thickness and vascular bundle integrity while modulating stomatal patterning and opening. However, growth and physiological function were still markedly hindered under severe salinity. Our multi-trait analysis demonstrates that rising CO2 may partially compensate for salinity impacts in maize, providing critical insights for predicting C4 crop stress resistance under future climate scenarios.

Long-standing alopecia areata is a therapeutically challenging subgroup lacking robust evidence regarding Janus kinase (JAK) inhibitors. This retrospective, single-centre study evaluated the efficacy and safety of baricitinib, tofacitinib or ritlecitinib in patients with current alopecia areata episodes lasting ≥8 years, treated between February 2021 and December 2025. Among 41 screened patients, 31 met the inclusion criteria (mean age 24.6±10.1 years; mean episode duration 12.7±4.6 years). The mean baseline SALT score was 62.8±30.2, with 64.5% of patients presenting a baseline SALT score ≥50. At week 24 (n=29), 27.6% and 24.1% of patients achieved absolute SALT scores ≤20 and ≤10, respectively. Relative improvements (SALT30, SALT50 and SALT80) were observed in 48.3%, 31.0% and 24.1% of patients. Treatment discontinuation occurred in 58.1% (18/31) of patients, primarily driven by a lack of efficacy (66.7% of these discontinuations). The most frequent adverse events were folliculitis (22.6%) and acne (12.9%). While the overall therapeutic response to JAK inhibitors remains limited in long-standing alopecia areata, a subset achieves clinically meaningful hair regrowth, supporting their use as a viable treatment option.

Despite advancements in systemic treatments, the efficacy of Janus kinase (JAK) inhibitors in acute versus non-acute alopecia areata (AA) remains poorly defined, necessitating comparative studies to optimize therapeutic strategies. This retrospective, single-centercentre cohort study included 158 AAalopecia areata patients treated with JAKJanus kinase inhibitors (tofacitinib or ritlecitinib) between 2021 and 2025, aimed at evaluating clinical outcomes and identifying predictors of super-responder (SR) status. Patients were stratified into acute (n=41) and non-acute (n=117) groups based on disease duration and treatment history, with efficacy assessed using the Severity of Alopecia Tool (SALT) through week 24. Our findings demonstrate that patients with acute AAalopecia areata achieved significantly superior outcomes, with 65 % reaching SALT100 by week 24 compared to 39.5 % in the non-acute group (p=0.041). Binary logistic regression analysis further identified tofacitinib treatment (OR=2.883, p=0.009) and mild-to-moderate baseline severity (OR=2.802, p=0.015) as significant predictors of SRsuper-responder status, while acute AAalopecia areata status showed borderline predictive value (OR=2.418, p=0.098). Although limited by its single-centercentre design and sample size, this study underscores that early intervention with JAKJanus kinase inhibitors in acute AAalopecia areata leads to enhanced hair regrowth, emphasizing the critical importance of timely clinical management.

Lupus erythematosus (LE) skin lesions are associated with significant dysregulation of the local immune microenvironment. However, the spatial distribution and interactions between stromal and immune cells within affected tissues remain poorly characterized. In this study, we employed Stereo-seq to construct a single-cell resolution spatial transcriptomic atlas of lesional skin from patients with discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE). Our analysis revealed that keratinocyte subpopulations in distinct differentiation states presented cell type-specific profiles of inflammatory mediator expression. Notably, a subset of stress keratinocytes located predominantly at the epidermis-dermis interface mediated the recruitment of T cells and plasma cells, potentially through an IFN-γ-JAK-STAT axis driving CXCL9/10/11-CXCR3 signaling, and these effects were more pronounced in active SLE lesions compared to chronic DLE lesions. Spatial profiling revealed immune cell niches resembling tertiary lymphoid structures (TLS), which were particularly prominent in chronic DLE and SLE lesions. These lupus-associated TLS structures were characterized by the coordinated infiltration of multiple cell subsets, including age-associated B cells, precursors of germinal center B cells, naïve B cells, regulatory T cells, T peripheral helper and/or T follicular helper cells, memory T cells, and CCL14+ vascular endothelial cells, which presented the spatial characteristics of the lymphoid follicle-like structures in chronic LE skin lesions. Collectively, our findings provide a comprehensive spatial characterization of the cellular components and molecular features within LE skin lesions.

BACKGROUND:Ritlecitinib represents the sole therapeutic agent currently approved for adolescents aged 12 to 17 years with severe alopecia areata (AA). Despite its regulatory endorsement, real-world data characterizing treatment outcomes and tolerability profiles in pediatric populations remain conspicuously absent. OBJECTIVE:To systematically assess clinical response trajectories and treatment-emergent adverse events among adolescent AA patients treated with ritlecitinib in a real-world clinical cohort. METHODS:We conducted a retrospective review of electronic medical records from December 2023 to May 2025, including AA patients aged 12 to 17 years treated with ritlecitinib. Data collected included demographics, AA severity scores [Severity of Alopecia Tool (SALT)], Eyebrow Assessment, Eyelash Assessment, and safety outcomes. RESULTS:The study enrolled 30 patients aged 12 to 17 years, with a median baseline SALT score of 61.3 (interquartile range 40.5-88.25). Treatment was administered over a 36 week period. By week 36, clinically meaningful improvements in SALT scores were observed: 96.7% of patients achieved at least a 30% reduction, while 86.7% and 70.0% attained reductions of ≥50% and ≥80%, respectively. At this time point, 24 patients (80.0%) achieved SALT scores ≤20. Among patients with baseline eyebrow or eyelash involvement, sustained regrowth was observed throughout the treatment period. All 6 patients with eyebrow involvement and all 5 with eyelash involvement exhibited complete recovery. Adverse events were predominantly mild, with folliculitis representing the most frequently reported event (n = 7). LIMITATIONS:Single-center, retrospective design. CONCLUSIONS:Real-world utilization of ritlecitinib demonstrated robust efficacy in AA while maintaining a favorable safety profile among adolescent populations, with no novel safety signals identified beyond established pharmacovigilance parameters.

Purpose/Aim of the Study Oral doxycycline (DOX) is a first-line systemic therapy for rosacea; however, persistent vascular features, such as fixed erythema and flushing, and neurosensory symptoms, such as burning, may respond incompletely to DOX alone. This study aimed to evaluate whether adding microneedling to oral DOX improves clinical outcomes in patients with rosacea.Materials and Methods This retrospective comparative cohort study included 160 patients with clinically confirmed rosacea. Patients received either 12 weeks of oral DOX monotherapy at 100 mg/day (control group, n = 80) or the same DOX regimen combined with three monthly microneedling sessions (intervention group, n = 80). The primary endpoint was the treatment success rate for facial erythema at week 12. Secondary outcomes included improvement in inflammatory papulopustular lesions, flushing, capillary dilation, swelling, burning sensations, quality of life, 6-month erythema relapse rate, and safety.Results At week 12, the intervention group showed a significantly higher treatment success rate for facial erythema than the control group (57.5% vs. 25.0%, p < 0.001). Improvement in inflammatory papulopustular lesions was substantial in both groups but did not differ significantly between them (75.0% vs. 70.0%, p = 0.478). Compared with DOX monotherapy, combination therapy produced significantly greater improvements in flushing, capillary dilation, swelling, burning sensations, and overall quality of life (all p < 0.01). The 6-month erythema relapse rate was also markedly lower in the intervention group than in the control group (20.0% vs. 68.4%, p < 0.001). No severe adverse events were observed.Conclusions Adding microneedling to oral DOX was associated with greater improvement in vascular and neurosensory manifestations of rosacea, particularly facial erythema, flushing, and burning sensations. The combination approach also reduced erythema relapse at 6 months and was well tolerated.

Aging, caused by a variety of exogenous stimuli and internal factors, leads to a gradual and irreversible decline in the function of the organism. The aging process involves complex gene regulation, in which transcription factors may play a key role as core regulatory elements. In this study, the single-cell transcriptome of skin revealed homeobox C10 (HOXC10) as a core element in the transcription factor regulatory network associated with skin aging. In vivo and vitro, the expression of HOXC10 was down-regulated in senescent fibroblasts and aging tissues, and overexpressed HOXC10 delayed cell senescence and skin aging. Mechanistically, HOXC10 targeted the promoter region of frizzled 6 (FZD6) to reduce its expression and therefore activated the Wnt/β-catenin signaling pathway to delay aging. Finally, by using the Connectivity Map approach, we explored simvastatin as a functional mimic of HOXC10 and demonstrated its antiaging ability in vitro and vivo. In conclusion, our results establish the role of HOXC10/FZD6/Wnt signals in skin aging and identify simvastatin as a potential therapeutic strategy to delay aging.